The nucleotide exchange factors of Hsp70 molecular chaperones.

Molecular chaperones of the Hsp70 family form an important hub in the cellular protein folding networks in bacteria and eukaryotes, connecting translation with the downstream machineries of protein folding and degradation. The Hsp70 folding cycle is driven by two types of cochaperones: J-domain proteins stimulate ATP hydrolysis by Hsp70, while nucleotide exchange factors (NEFs) promote replacement of Hsp70-bound ADP with ATP. Bacteria and organelles of bacterial origin have only one known NEF type for Hsp70, GrpE. In contrast, a large diversity of Hsp70 NEFs has been discovered in the eukaryotic cell. These NEFs belong to the Hsp110/Grp170, HspBP1/Sil1, and BAG domain protein families. In this short review we compare the structures and molecular mechanisms of nucleotide exchange factors for Hsp70 and discuss how these cochaperones contribute to protein folding and quality control in the cell

Lower urinary tract symptoms secondary to mass lesion of the brain: A case report

Intracranial mass lesions presenting secondary to neurologic disorders are well established but are rarely causes of lower urinary tract symptoms (LUTS). Only a very few cases were described in the literature. We present a 64‑year‑old woman with urinary urgency, frequency, and incontinence, which were secondary to a large meningioma along the anterior falx. New‑onset neurologic symptoms presenting as any unusual clinical presentations of LUTS should be explored to rule out potentially treatable causes before making decisions for uro‑gynecological interventions.Keywords: Brain tumor; frontal lobe; lower urinary tract symptoms; neurologic disorde

Food waste opportunities within the food wholesale and retail sectors

The aim of this research project is to provide the NSW Environment Protection Authority (NSW EPA) with a better understanding of the opportunities and barriers to reduce the amount of food waste going to landfill from the wholesale, logistics and retail sector. This report presents the research findings and provides a series of recommendations as to how NSW EPA can most effectively engage with these sectors within the food supply chain to maximise performance while minimising disruption and costs

Alternative mechanisms of structuring biomembranes: Self-assembly vs. self-organization

We study two mechanisms for the formation of protein patterns near membranes of living cells by mathematical modelling. Self-assembly of protein domains by electrostatic lipid-protein interactions is contrasted with self-organization due to a nonequilibrium biochemical reaction cycle of proteins near the membrane. While both processes lead eventually to quite similar patterns, their evolution occurs on very different length and time scales. Self-assembly produces periodic protein patterns on a spatial scale below 0.1 micron in a few seconds followed by extremely slow coarsening, whereas self-organization results in a pattern wavelength comparable to the typical cell size of 100 micron within a few minutes suggesting different biological functions for the two processes.Comment: 4 pages, 5 figure

Gait and Cognition: A Complementary Approach to Understanding Brain Function and the Risk of Falling

Until recently, clinicians and researchers have performed gait assessments and cognitive assessments separately when evaluating older adults, but increasing evidence from clinical practice, epidemiological studies, and clinical trials shows that gait and cognition are interrelated in older adults. Quantifiable alterations in gait in older adults are associated with falls, dementia, and disability. At the same time, emerging evidence indicates that early disturbances in cognitive processes such as attention, executive function, and working memory are associated with slower gait and gait instability during single- and dual-task testing and that these cognitive disturbances assist in the prediction of future mobility loss, falls, and progression to dementia. This article reviews the importance of the interrelationship between gait and cognition in aging and presents evidence that gait assessments can provide a window into the understanding of cognitive function and dysfunction and fall risk in older people in clinical practice. To this end, the benefits of dual-task gait assessments (e.g., walking while performing an attention-demanding task) as a marker of fall risk are summarized. A potential complementary approach for reducing the risk of falls by improving certain aspects of cognition through nonpharmacological and pharmacological treatments is also presented. Untangling the relationship between early gait disturbances and early cognitive changes may be helpful in identifying older adults at risk of experiencing mobility decline, falls, and progression to dementia. J Am Geriatr Soc 60: 2127-2136, 2012

Chemopreventive Potential of Synergy1 and Soybean in Reducing Azoxymethane-Induced Aberrant Crypt Foci in Fisher 344 Male Rats

Synergy1, a prebiotic composed of Inulin and Oligofructose (1 : 1). Soybean meal is a natural source of isoflavones. The objective was to investigate the effects of feeding Synergy1 and SM on the incidence of azoxymethane- (AOM-) induced aberrant crypt foci (ACF) in Fisher 344 male rats. Rats (54) were randomly assigned to 9 groups (n = 6). Control group (C) was fed AIN-93G and treatment groups Syn1 and SM at 5% and 10% singly and in combinations. Rats were injected with two s/c injections of AOM at 7 and 8 weeks of age at 16 mg/kg body weight and killed at 17 weeks by CO2 asphyxiation. Colonic ACF enumeration and hepatic enzyme activities were measured. Reductions (%) in total ACF among treatment groups fed combinations were higher (67–77) compared to groups fed singly (52–64). Synergistic mechanisms among phytochemicals may be responsible suggesting protective role in colon carcinogenesis with implications in food product development

Combinational Effects of Prebiotics and Soybean against Azoxymethane-Induced Colon Cancer In Vivo

Prebiotic fructans are nondigestible carbohydrates with numerous health benefits. Soybean is a rich source of phytonutrients such as isoflavones. The objective of this study was to evaluate the chemopreventive effects of prebiotics (Synergy1) and soybean meal (SM) at 5% and 10% levels alone and in combination on azoxymethane- (AOM-) induced colon carcinogenesis. After one wk of acclimatization, Fisher 344 male rats (N = 90) were randomly assigned to 9 groups (n = 10). Control rats (C) were fed AIN-93G/M. Two s/c injections of AOM were administered to rats at 7 and 8 wk of age at 16 mg/kg body weight. Rats were killed by CO2 asphyxiation at 45 wk. Tumor incidence (%) in treatment groups ranged from 40 to 75 compared to 100 in C. Results indicate that feeding prebiotics and soybean in combination significantly reduced incidence of AOM-induced colon tumors with implications for food industry in the food-product development

Continuous quantitative monitoring of cerebral oxygen metabolism in neonates by ventilator-gated analysis of NIRS recordings

Oxidative stress during fetal development, delivery, or early postnatal life is a major cause of neuropathology, as both hypoxic and hyperoxic insults can significantly damage the developing brain. Despite the obvious need for reliable cerebral oxygenation monitoring, no technology currently exists to monitor cerebral oxygen metabolism continuously and noninvasively in infants at high risk for developing brain injury. Consequently, a rational approach to titrating oxygen supply to cerebral oxygen demand – and thus avoiding hyperoxic or hypoxic insults – is currently lacking. We present a promising method to close this crucial technology gap in the important case of neonates on conventional ventilators. By using cerebral near-infrared spectroscopy and signals from conventional ventilators, along with arterial oxygen saturation, we derive continuous (breath-by-breath) estimates of cerebral venous oxygen saturation, cerebral oxygen extraction fraction, cerebral blood flow, and cerebral metabolic rate of oxygen. The resultant estimates compare very favorably to previously reported data obtained by non-continuous and invasive means from preterm infants in neonatal critical care.National Institutes of Health (U.S.) (Grant R01EB001659)National Institutes of Health (U.S.) (Grant K24NS057568)National Institutes of Health (U.S.) (Grant R21HD056009

Capacity limitations of visual memory in two-interval comparison of Gabor arrays

The capacity of short-term visual memory (VSTM) was assessed in a two-interval spatial frequency (SF) discrimination task. The cued Gabor target in a multi-element array either increased or decreased in SF across a 2s interstimulus interval (ISI). Distracters as well as target were made to change across ISI so that memory of the individual SF of Gabor elements was required to solve the discrimination. The dynamics of the information loss from visual memory were analysed by manipulating the timing of spatial cues and masks. Cueing the target position before the first display gave thresholds comparable with those for a single Gabor patch. Cues placed after the first display gave higher thresholds indicating some loss of information. Within the ISI there was little increase in threshold or set size effect with cue delay. However there was a sharp rise in thresholds for cue positions after the second display. Gabor masks placed before a mid-ISI cue were more effective than noise masks or Gabor masks placed after the cue. With a cue placed late in the ISI, preceded by a Gabor mask, the masking effect decreased with increasing delay of the mask after the first display. This suggests a selective, dynamic but increasingly durable representation of the initial stimulus is built up in memory, and there is a graded form of “overwriting” of this representation by new stimuli

Examining links between anxiety, reinvestment and walking when talking by older adults during adaptive gait

Falls by older adults often result in reduced quality of life and debilitating fear of further falls. Stopping walking when talking (SWWT) is a significant predictor of future falls by older adults and is thought to reflect age-related increases in attentional demands of walking. We examine whether SWWT is associated with use of explicit movement cues during locomotion, and evaluate if conscious control (i.e., movement specific reinvestment) is causally linked to falls-related anxiety during a complex walking task. We observed whether twenty-four older adults stopped walking when talking when asked a question during an adaptive gait task. After certain trials, participants completed a visual-spatial recall task regarding walkway features, or answered questions about their movements during the walk. In a subsequent experimental condition, participants completed the walking task under conditions of raised postural threat. Compared to a control group, participants who SWWT reported higher scores for aspects of reinvestment relating to conscious motor processing but not movement self-consciousness. The higher scores for conscious motor processing were preserved when scores representing cognitive function were included as a covariate. There were no group differences in measures of general cognitive function, visual spatial working memory or balance confidence. However, the SWWT group reported higher scores on a test of external awareness when walking, indicating allocation of attention away from task-relevant environmental features. Under conditions of increased threat, participants self-reported significantly greater state anxiety and reinvestment and displayed more accurate responses about their movements during the task. SWWT is not associated solely with age-related cognitive decline or generic increases in age-related attentional demands of walking. SWWT may be caused by competition for phonological resources of working memory associated with consciously processing motor actions and appears to be causally linked with fall-related anxiety and increased vigilance.This research was supported by The Royal Society (IE131576) and British Academy (SG132820)